Multifunctional Thermosensitive Liposomes Based on Natural Phase-Change Material: Near-Infrared Light-Triggered Drug Release and Multimodal Imaging-Guided Cancer Combination Therapy

ACS Appl Mater Interfaces. 2019 Mar 20;11(11):10540-10553. doi: 10.1021/acsami.8b22748. Epub 2019 Mar 8.

Abstract

Multifunctional theranostic nanoplatforms (NPs) in response to environment stimulations for on-demand drug release are highly desirable. Herein, the near-infrared (NIR)-absorbing dye, indocyanine green (ICG), and the antitumor drug, doxorubicin (DOX), were efficiently coencapsulated into the thermosensitive liposomes based on natural phase-change material. Folate and conjugated gadolinium (Gd) chelate-modified liposome shells enhance active targeting and magnetic resonance performance of the NPs while maintaining the size of the NPs. The ICG/DOX-loaded and gadolinium chelate conjugated temperature-sensitive liposome nanoplatforms (ID@TSL-Gd NPs) exhibited NIR-triggered drug release and prominent chemo-, photothermal, and photodynamic therapy properties. With the coencapsulated ICG, DOX, and the conjugated gadolinium chelates, the ID@TSL-Gd NPs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging)-guided combination tumor therapy (chemotherapy, photothermotherapy, and photodynamic therapy). After tail vein injection, the ID@TSL-Gd NPs accumulated effectively in subcutaneous HeLa tumor of mice. The tumor was effectively suppressed by accurate imaging-guided NIR-triggered phototherapy and chemotherapy, and no tumor regression and side effects were observed. In summary, the prepared ID@TSL-Gd NPs achieved multimodal imaging-guided cancer combination therapy, providing a promising platform for improving diagnosis and treatment of cancer.

Keywords: combination therapy; liposomes; multimodal imaging; phase-change material; thermosensitive.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Female
  • Folic Acid / chemistry
  • Gadolinium / chemistry
  • HeLa Cells
  • Humans
  • Indocyanine Green / chemistry
  • Indocyanine Green / pharmacology
  • Indocyanine Green / therapeutic use
  • Infrared Rays*
  • Liposomes / chemistry*
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Nude
  • Nanostructures / chemistry*
  • Nanostructures / toxicity
  • Neoplasms / diagnostic imaging
  • Neoplasms / drug therapy
  • Neoplasms / therapy*
  • Photochemotherapy
  • Phototherapy
  • Reactive Oxygen Species / metabolism
  • Transplantation, Heterologous

Substances

  • Liposomes
  • Reactive Oxygen Species
  • Doxorubicin
  • Folic Acid
  • Gadolinium
  • Indocyanine Green